The American Cancer Society predicted that 240,890 new men will be diagnosed with prostate cancer in 2011 and another 33,720 men will die of this disease, which makes prostate cancer the second leading cause of cancer related death in men in the United States.1 Surgical removal of the prostate gland and pelvic lymph nodes, which is known as radical prostatectomy (RP) provides excellent control for clinically localized prostate cancer.2 However, one-third of prostate cancer patients undergoing RP show positive surgical margins, another 9% will have seminal vesicle invasion, and one-third show extracapsular extension,3-6 which are pathological risk factors for cancer recurrence. Indeed, 40%-50% of high risk patients show biochemical recurrence (i.e. serum concentration of prostate specific antigen (PSA) is ≧0.2 ng/mL)7 after RP and many of those patients develop metastases.8-13 
Recent investigations have shown therapeutic benefits in applying radiation therapy locally to the prostate fossa in patients showing biochemical recurrence after RP, which is known as salvage radiotherapy (SRT).14-16 A retrospective analysis of 635 prostate cancer patients who either received SRT alone (n=160), SRT combined with hormonal therapy (n=78), or no salvage treatment (n=397) showed a 10-year prostate cancer-specific survival rate of 86% in patients treated with SRT compared to a survival rate of 62% in patients who were not treated with SRT indicating a 3-fold increase in prostate cancer-specific survival in repose to local SRT.16 Another retrospective analysis used a cohort of 1,540 prostate cancer patients to develop a model to predict biochemical control of prostate cancer after SRT,15 which clearly showed that 60%-70% of patients with recurrent prostate cancer develop metastasis within 6 years if they do not receive SRT.17 These data evidence that local ablation of recurrent prostate cancer cells using SRT alters the natural course of the disease and prevent its metastatic spread.
Clinical guidelines for SRT advocate the treatment of the vesicourethral anastomosis and the surrounding periurethral tissues but differ as to the volume of the bladder and seminal vesicle beds that should be irradiated.18-20 Consequently, SRT is routinely applied to large tissue volumes centered around the prostatic fossa,21-23 which results in multiple acute and delayed toxicities such as diarrhea, proctitis, cystitis, urethral strictures, urinary urgency, and rectal complications.22,24,25 Furthermore, patients who received SRT after RP experienced worse sexual functioning compared to those who had RP alone, which is probably due to radiation damage of the vascular structure of the penis.26-28 Collectively, these studies indicate the therapeutic benefit of local ablation of recurrent prostate cancer cells as an effective strategy to suppress the development of the metastatic disease but also demonstrate the need for achieving selective eradication of prostate cancer cells without damaging neighboring healthy tissue.